NIDA has taken a lead role in developing the scientific basis of drug testing.

The scientific "validity" of a test system is determined by numerous chemical (e.g., sensitivity,
specificity) and pharmacological factors (e.g., dose, frequency of use). It is vital to research
these factors for each existing and new test system to insure that test systems are fair, accurate
and reproducible.

In addition to conventional urine testing, other biological materials (e.g., saliva, sweat, hair) may
be useful for drug testing. Research on these new technologies is underway at NIDA and other
institutions.

Research has shown that each biological fluid and tissue provides unique and sometimes
different information regarding an individual's drug exposure history.

Saliva testing provides a reasonable alternative to blood testing and offers similar information
regarding possible influence of drugs on the person at the time of testing (e.g., drugged driver
testing). Collection is relatively non-invasive, but drug detection times are short.

Sweat testing with a "patch" device offers a non-invasive way to monitor drug use over a weekly
interval. Caution must be practiced not to contaminate the patch when applying or removing it.

Hair testing offers a long term "historical" look at an individual's drug exposure over a period of
months. Environmental contamination and hair color bias for certain drugs is of concern.
Advantages include the long term detection of drug and ability to obtain a similar specimen days
after collection of an original specimen.

Mr. Chairman and Members of the Subcommittee, I am Dr. Edward J. Cone, Acting Chief of the
Clinical Pharmacology Branch, Intramural Research Program, National Institute on Drug Abuse
(NIDA), one of the research Institutes of the National Institutes of Health. I am very pleased to
be here today with my distinguished colleagues to testify before the Subcommittee.

The National Institute on Drug Abuse supports over 85 percent of the world's research on
the health aspects of drug abuse and addiction. For more than two decades, NIDA has been
exploring the biomedical and behavioral foundations of drug abuse. NIDA's scientific research
program addresses the most fundamental and essential questions about drug abuse, ranging from
its causes and consequences to its prevention and treatment. The scientific knowledge that is
generated through NIDA research is a critical element to improving the overall health of the
Nation. There has never been a greater need to increase our knowledge about drug abuse. I am
very pleased to be able to testify today on current research findings concerning the comparative
usefulness of various biological samples for drug detection (See Table 1).

General Issues About Drug Testing

Drug testing technology, such as urinalysis, provides an objective means of determining
recent drug use. The scientific basis of drug testing has been advancing rapidly over the last two
decades resulting in the commercial development of reliable and inexpensive urine-based tests.
At the same time research has been progressing on the evaluation of other biological fluids and
tissues for drug detection. NIDA has taken a lead role in researching the utility of various
biological samples as substrates for drug testing. NIDA staff have published over 20 scientific
papers on the possible use of hair, sweat, saliva, sebum, skin, meconium and other specimens for
drug testing. As a result of advances in the science of drug testing, there is growing commercial
interest in utilizing saliva, sweat, hair and meconium for the detection of drug use.

The usefulness of a drug test resides in its ability to accurately detect the presence of the
parent drug and/or its metabolite(s) in a biological fluid or tissue following human drug use.
Many factors can influence the "validity" of these test systems. The accuracy of drug testing
reflects both chemical factors which influence test outcome, such as sensitivity (the least amount
of detectable drug) and specificity (how selective the test is for the drug) as well as
pharmacological considerations such as drug dose, time of drug use and route of drug
administration. Individual differences in rate of absorption, metabolism and excretion are
additional pharmacological variables that can influence the test outcome.

In the development of drug testing systems, it is paramount that the results are accurate,
reliable, and free from the possibility of bias towards different populations. Therefore, the test
system must demonstrate that it performs its intended purpose, that it accurately identifies drug
users, and it does not falsely incriminate innocent people. Numerous scientific principles and
guidelines have evolved that new as well as existing drug testing technologies should follow. In
order for a new biological material, such as hair, to be useful for drug testing, the tests using that
material should have the following attributes:

the biological material to be tested should be easily obtainable and as non-invasive as
possible;

the drug and/or its metabolite should be present in the biological material and be
identified accurately and precisely with existing, available technology;

the amount of the drug and/or metabolite appearing the biological material following
the use of a single psychoactive dose of a drug should be sufficient for routine detection (that is,
there should be a low rate of false negative results);

the relationship between concentration of drug and/or metabolite and the drug dose
taken should be clearly established;

the time course of appearance and disappearance of the drug in the material should be
clearly established and matched to the purpose or intent of testing (e.g. detection of recent or
long-term drug use);

the risk of false positive results from environmental contamination should be
extremely small;

the drug test methodology should be completely unbiased toward all populations and
ethnic groups--this is not to say that individual differences in rates of metabolism and excretion
should not exist, but simply that test methodology as a whole should not produce a higher overall
rate of positive (or negative) results for any particular ethnic or minority group compared to the
general population.

At the present time, there are a plethora of commercial assays and published
methodologies that may be employed for drug testing. For the most part, these methods can be
grouped into two categories, screening assays (tests) and confirmation assays. These assays can
be adapted for measurement of drugs in body fluids, but they must first be properly validated.
Generally, screening assays, such as immunoassays, are commercial-based tests that are
inexpensive and simple to perform. In contrast, confirmation assays, such as gas
chromatography/mass spectrometry (GC/MS), are more expensive and more labor intensive, but
the sensitivity and specificity are generally higher than the screening assays.

Immunoassay screening tests may cross-react with a variety of similar chemical
substances, reducing their specificity. For example, most commercial immunoassays for opiates
give positive test results for specimens containing either morphine, codeine or heroin
metabolites. In this case, a more specific methodology, i.e. a confirmation assay, is needed to
identify the particular drug or metabolite present. Often, the less expensive screening tests are
employed initially to eliminate specimens containing no drug or drug below the cutoff
concentration. The more expensive, labor intensive tests are subsequently employed for absolute
drug identification and accurate quantification.

Urine Testing

When a drug is taken intravenously or smoked, the absorption of the drug into the body is
nearly instantaneous and its excretion in urine begins almost immediately. Drug absorption into
the body is slower when the drug is taken orally and its excretion in urine may be delayed for
several hours. Normally, urine specimens voided within six hours after taking a drug contain the
highest concentration of the drug and its metabolites. In general, drug excretion in urine occurs
at an exponential rate with most of the drug being eliminated within 48 hours after
administration. Detection times for drugs of abuse vary according to dose, frequency of taking
the drug, cutoff concentration and numerous other factors. Despite this variability, average
detection time for most drugs in urine range from one to five days when the user is taking low
doses or is an occasional user. When the individual is a heavy, chronic drug user, the detection
times for some drugs, e.g. marijuana, may be up to a month.

Saliva

Considerable research has been focussed on the utility of saliva as a biological material
for drug testing. Saliva offers a number of advantages and some disadvantages in comparison to
urine testing. The major advantages include its easy accessibility for collection, less
objectionable nature (compared to urine), presence of the parent drug in higher abundance than
metabolites, and a high correlation between the concentration of drug found in the blood and that
which is detected in saliva. Further, studies have found that the amount of cocaine detected in
saliva correlates strongly with the physiological and euphoric effects of cocaine including the
heart rate and self-reported feelings of cocaine "rush."

Despite the numerous advantages of saliva, there are some disadvantages. For example,
there is a risk of contamination of saliva from drug use by the oral, smoked, and intranasal
routes. This contamination can skew the correlation between saliva and blood drug
concentrations, thereby distorting useful pharmacokinetic relationships. Even with this obvious
limitation, saliva measurements can be used as evidence of recent drug use, even in some
situations in which oral contamination is likely to be involved, e.g. marijuana smoking.

Another disadvantage of the use of saliva for drug testing, is the short time course for
detectability of drugs. This effectively prevents saliva from being used to detect historical drug
use. At the same time, however, this feature makes saliva useful for detection of very recent
drug use. Most drugs disappear from saliva and blood within 12-24 hours after administration.
However, there is often a temporal relationship between the disappearance of drugs in saliva and
the duration of its pharmacologic effects. Consequently, saliva testing could be useful in the
detection of recent drug use in automobile drivers, accident victims and for testing employees
prior to engaging in safety-sensitive activities.

Sweat

Research on sweat testing for drugs has been limited because of the difficulty in
collecting sweat samples. Recently, a sweat collection device has been developed that appears to
offer promise for drug monitoring. This device resembles a Band-Aid which is applied to the
skin and can be worn for a period of several days to several weeks. The "sweat patch" consists
of an adhesive layer on a thin transparent film of surgical dressing to which a rectangular
absorbent cellulose pad is attached. Sweat is absorbed and concentrated on the cellulose pad.
The transparent film allows oxygen, carbon dioxide and water vapor to escape, but prevents loss
of drug constituents excreted in an individual's sweat. Over a period of several days, sweat
saturates the pad and the excreted drug slowly concentrates. The patch can then be removed, the
absorbent pad detached from the device and analyzed for drug content.

The advantages of the sweat patch for drug monitoring include the high subject
acceptability of wearing the patch, low incidence of allergic reactions to the patch adhesive, and
the ability to monitor drug intake for a full week with a single patch. In addition, the patch
appears to be relatively tamper-proof in that the patch adhesive is specially formulated so that the
patch can only be applied once and cannot be removed and successfully reapplied to the skin
surface.

Disadvantages of the sweat patch include high variability among individuals, possibility
of environmental contamination of the patch before application or after removal, and risk of
accidental removal during a monitoring period. During patch application, extreme care must be
taken to cleanse the skin surface prior to placement of the patch and also avoid contamination of
the cellulose pad during handling. Similar care must be taken when removing the patch and
handling for analysis. Since this is a relatively new technology, research is ongoing into the
efficacy and utility of sweat as a biological material for drug testing.

Hair

The use of hair as a biological material for drug testing has received much attention over
the last decade. While the technology of hair testing has progressed rapidly, there remain several
highly controversial aspects of hair testing yet to be worked out. First and probably foremost, it
is unclear how drugs enter hair. The most likely routes involve:

diffusion from blood into the hair follicle and hair cells with subsequent binding
to hair cell components,

excretion in sweat which bathes hair follicles and hair strands,

excretion of oily secretions into the hair follicle and onto the skin surface,

entry from the environment.

The possibility of drug entry from sweat and/or the environment are particularly troubling since
this allows the possibility of false positives if an individual's hair absorbs drugs from the
environment or from another person's drug-laden sweat.

Another controversial issue in hair analysis is the interpretation of dose and time
relationships. Although it has been generally assumed that segmental analysis of hair provides a
record of drug usage, studies with labeled cocaine have not supported this interpretation. At best,
only limited dose and time relationships were found. Other controversial issues that remain
unresolved are the possibility of bias based on hair color and texture, appropriate means of
differentiating drug users' hair from environmentally contaminated hair, appropriate applications
of hair testing and the feasibility of hair testing for marijuana usage.

Despite the controversial nature of some aspects of hair testing, this technique is being
used on an increasingly broad scale in a variety of circumstances. One of the most promising
applications of hair testing appears to be its use in epidemiological studies of drug use. Hair
testing could be a valuable confirmation of the self-reported drug use data that much of the
current research in this area relies upon. In addition, the time record of drug use available from
hair is considerably longer than any other biological materials currently being employed for drug
testing. Self-reported drug use over a period of several months can be compared to test results
from a hair strand representative of the same time period (about 4 cm in this case) as a means of
validating the self-report data. It is expected that this type of comparison would be more
effective than urine testing since urine provides a historical record of only two to four days under
most circumstances.

Other advantages include ease of obtaining, storing and shipping specimens, ability to
obtain a second sample for reanalysis, low potential for evasion or manipulation of test results,
and low risk of disease transmission in the handling of samples.

A potential disadvantage of hair analysis would be its inability to detect recent drug usage
because of slow growth rate. However, this has not been thoroughly investigated. Recent
evidence suggests that drug excretion in sweat is an important route of drug entry into the hair.
This allows for the possibility that drug could appear in the hair within hours of drug
administration. Another consideration regarding the use of hair analysis is the limited number of
laboratories offering commercial hair testing services. However, as demand for hair testing
services grows, commercial development will expand to meet that demand. As more attention is
then focused on this new area of drug testing, and further research is conducted, perhaps many of
the early controversies will eventually be resolved.